MECHANISMS OF CANCER BIOLOGY PROGRAM (MCBP): PROJECT SUMMARY The long-term goal of the Mechanisms of Cancer Biology Program (MCBP) is to identify and map the complex cellular mechanisms that drive cancer development, progression, and metastasis. To accomplish this goal, members of the MCBP are identifying factors (biochemical and physical), signaling pathways and the cellular basis for the communication between tumor and stromal cells that drives tumorigenesis. Together this approach will lay the framework for the design of specific therapeutic modalities. The MCBP is organized around two working groups termed the, (1) Cell Autonomous Cancer Drivers (CACD) and (2) Cancer Cell Nonautonomous Drivers (CCND). Recognizing the importance of the co-morbidities associated not only with the disease but the treatments deployed to fight it, MCBP is developing a third group referred to as Cancer Co-Morbidity Drivers (CCMD). Together these thematic groups include individuals working to discover how cell autonomous mutations and stromal cells, extracellular matrix structural proteins, growth factors, and cytokines interact to modulate tumorigenesis. Further, as cancer therapies become more effective at reducing mortality, cancer survivors are increasingly faced with therapy-induced co-morbidities that can significantly impact their quality of life. Thus, MCBP members also focus on the mechanisms that drive therapy-induced co-morbidities. The MCBP primarily performs basic cancer biology research and discovery, and is structured to interface with other programs within the Siteman Cancer Center (SCC) that are positioned to translate research breakthroughs into patient care, particularly in genetics, molecular and cellular cancer biology, and functional genomics. The MCBP members are currently developing a number of therapeutic drugs that were identified using this approach, which are discussed in the body of the grant. The MCBP is dedicated to achieving the following two goals: (1) identify key molecules and pathways (i.e., targets) within tumor cells and the tumor-stromal interactions that regulate tumor cell proliferation, survival, and metastasis, and develop therapeutic strategies to target these key molecules and/or pathways; and (2) develop select inter-programmatic working groups to facilitate the translation of the results from Goal 1. Each working group focuses on the central importance of intracellular communication within incipient tumor cells and intercellular communication between tumor cells and the stromal microenvironment. Each member has specific expertise and shared goals that are utilized to develop a robust research program with strong intra- and inter- programmatic collaborations. MCBP has 40 members from 12 departments and three schools, and is supported by $15.1 million in funding, with $4.3 million from the NCI and $7.2 million from other peer-reviewed funding sources. MCBP members published 711 peer-reviewed papers during 2014?2018, with 142 (20%) papers in journals with impact factors ?10. MCBP members also engaged in extensive collaborative interactions, with 172 (24%) inter- and 108 (15%) intra-programmatic publications.